Granulation tissue formation

Histopathology of Granulation tissue

1. Granulation tissue formation Dr Mohammad Manzoor Mashwani Healing: 1. Regeneration 2. Repair Repair: 1. Granulation tissue formation 2. Contraction of wounds A Young Scar Granulation tissue is highly vascularized connective tissue composed of newly formed capillaries , proliferating fibroblasts and residual inflammatory cells . Cell injury is defined as a variety of stresses a cell encounters as a result of changes in its internal and external environment.

2. Healing Healing is the body response to injury in an attempt to restore normal structure and function. Healing involves 2 distinct processes: Regeneration Repair

3. Healing by Regeneration Regeneration when healing takes place by proliferation of parenchymal cells and usually results in complete restoration of the original tissues. OR The replacement of the destroyed tissue by the parenchymal cells of the same type is called regeneration. OR The replacement of destroyed cells by proliferation of surrounding undamaged cells of the same type is called regeneration.

4. Regenerative capacity of different cell types The cells of the body are divided into three groups on the basis of their regenerative capacity as following: 1. Labile cells or continuously dividing cells: 2. Stable cells or Quiescent cells 3. Permanent cells or Non-dividing cells Control of Cell growth: by growth factors.

5. Healing by REPAIR Repair when healing takes place by proliferation of connective tissue elements r esulting in fibrosis and scarring . At times, both the processes (Regeneration & Repair) take place simultaneously. Repair is the replacement of injured tissue by fibrous tissue. Repair is the process by which lost or destroyed cells are replaced by viable cells.

6. REPAIR Two processes are involved in repair: 1. Granulation tissue formation ; and 2. Contraction of wounds . Repair response takes place by participation of Mesenchymal cells (consisting of connective tissue, stem cells, fibrocytes and histiocytes), Endothelial cells, Macrophages, Platelets, and the Parenchymal cells of the injured organ.

7. The conditions in which tissue healing is achieved by repair ( scar formation ): 1. When resolution (recovery) fails to occur in an acute inflammation. 2. When parenchymal cells necrosis cannot be repaired by regeneration because: i. Necrotic cells are permanent cells ii. Stable cells are destroyed iii. Necrosis is so extensive that no cells are available for regeneration.

8. A young scar Granulation tissue  is new connective tissue and tiny blood vessels that form on the surfaces of a wound during the healing process .   Granulation tissue typically grows from the base of a wound and is able to fill wounds of almost any size. The term granulation tissue derives its name from slightly granular and pink appearance of the tissue. Each granule corresponds histologically to proliferation of new small blood vessels which are slightly lifted on the surface by thin covering of fibroblasts and young collagen . Granulation tissue forms and fills the injured area while the necrotic debris is being removed . Granulation tissue is highly vascularized connective tissue composed of newly formed capillaries , proliferating fibroblasts and residual inflammatory cells .

9. Granuloma- a type of ch . Inf. Granuloma is defined as a circumscribed , tiny lesion, about 1 mm in diameter, composed predominantly of collection of modified macrophages called epithelioid cells, and rimmed at the periphery by lymphoid cells . The word ‘granuloma’ is derived from granule meaning circumscribed granule-like lesion , and -oma which is a suffix commonly used for true tumours but here it indicates a localised inflammatory mass or collection of macrophages. Granuloma: Collection of epithelioid cells rimed by lymphocytes .

10. Primary & secondary intensions Wound healing 1 intention Edges lined up     2 intention Edges not lined up Ergo…. More granulation More epithelialization More fibrosis

11. ` The following 3 phases are observed in the formation of granulation tissue : 1. PHASE OF INFLAMMATION . Following trauma, blood clots at the site of injury. There is acute inflammatory response with exudation of plasma , neutrophils and some monocytes within 24 hours. 2. PHASE OF CLEARANCE . Combination of Proteolytic enzymes liberated from neutrophils , autolytic enzymes from dead tissues cells , and phagocytic activity of macrophages clear off the necrotic tissue, debris and red blood cells.

12. 3. PHASE OF INGROWTH OF GRANULATION TISSUE This phase consists of 2 main processes: angiogenesis or neovascularisation , and fibrogenesis . Angiogenesis (neovascularisation). Formation of new blood vessels at the site of injury takes place by proliferation of endothelial cells from the margins of severed blood vessels . Initially, the proliferated endothelial cells are solid buds but within a few hours develop a lumen and start carrying blood . The newly formed blood vessels are more leaky , accounting for the oedematous appearance of new granulation tissue. Soon, these blood vessels differentiate into muscular arterioles, thin-walled venules and true capillaries .

13. The process of angiogenesis is stimulated with proteolytic destruction of basement membrane . Angiogenesis takes place under the influence of following factors: a) Vascular endothelial growth factor ( VEGF ) elaborated by mesenchymal cells while its receptors are present in endothelial cells only. b) Platelet-derived growth factor ( PDGF ), Transforming growth factor-β ( TGF-β ), basic fibroblast growth factor ( bFGF ) and surface integrins are all associated with cellular proliferation.

14. ii ) Fibrogenesis The newly formed blood vessels are present in an amorphous ground substance or matrix. The new fibroblasts originate from fibrocytes as well as by mitotic division of fibroblasts. Collagen fibrils begin to appear by about 6th day . As maturation proceeds, more and more of collagen is formed while the number of active fibroblasts and new blood vessels decreases. This results in formation of inactive looking scar known as cicatrisation . A  fibroblast   is a type of cell that synthesizes the extracellular matrix and collagen , the structural framework (stroma) for animal tissues, and plays a critical role in wound healing.  Fibroblasts  are the most common cells of connective tissue in animals.

15. Fibroblasts and  fibrocytes  are two states of the same cells, the former being the activated state, the latter the less active state, concerned with maintenance and tissue metabolism. Currently, there is a tendency to call both forms fibroblasts. The suffix "blast" is used in cellular biology to denote a  stem cell  or a cell in an activated state of  metabolism .

16. Gross Morphology During the migratory phase of wound healing, granulation tissue is: light red or dark pink in color, being perfused with new capillary loops or "buds "; soft to the touch ; moist; and bumpy (granular )/pebbly in appearance , due to punctate hemorrhages, pulseful on  palpation , painless when healthy .

17. Microscopy Microscopic examination shows thin-walled capillaries lined by endothelium and surrounded by fibroblasts . Residual inflammatory cells: Neutrophils, lymphocytes, plasma cells & macrophages

18. Active granulation tissue has inflammatory cell infiltrate, newly formed blood vessels and young fibrous tissue in loose matrix.

19. Fibronectin Fibronectin is a glycoprotein that plays a key role in the formation of granulation tissue and is present in large amount during wound healing. In early phases, it is derived from plasma , but later it is synthesized by fibroblasts, macrophages and endothelial cells in granulation tissue. Adhesion Protein Fibrillar structural proteins (collagen, elastin); Adhesion proteins ( fibronectin, laminin, fibrillin, osteonectin, tenacin); and

20. Fibrosis (Collagenization) Collagen is the major fibrillary protein of connective tissue. It is synthesized by fibroblast and is responsible for much of tensile strength of scar tissue. The term fibrous tissue and scar tissues are synonymous with collagen. Fibrillar structural proteins (collagen, elastin); Adhesion proteins ( fibronectin, laminin, fibrillin, osteonectin, tenacin); and

21. Methionin Proteins are needed for the process of healing. Methionin (an amino acid) is essential for building up of granulation tissue. In protein deficiency granulation tissue and collagen production is delayed, resulting in weak scar .

22. Vitamin C Vitamin C is essential for the synthesis of collagen fibers. In vitamin C deficiency fibroblasts produce little collagen , therefore, healing is poor and delayed.

23. Maturation of Scar h As the scar matures the amount of collagen increases and the scar becomes less cellular and less vascular . The mature scar is composed of an avascular, poorly cellular mass of collagen and is white on gross examination.

24. Proud flesh Formation of excessive amount of granulation tissue which protrudes above the level of the surrounding skin , is called proud flesh.

25. Example of granulation tissue from a cut on a finger with "proud flesh ".

26. Contraction of Wound Contraction decreases the size of scar and enables the surviving cells of the organ to function with maximum effectiveness .

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